Integrating patients in time series clinical transcriptomics data

Author:

Hasanaj Euxhen1ORCID,Mathur Sachin2ORCID,Bar-Joseph Ziv123ORCID

Affiliation:

1. Machine Learning Department, Carnegie Mellon University , Pittsburgh, PA 15213, United States

2. R&D Data and Computational Sciences, Sanofi , Cambridge, MA 02141, United States

3. Computational Biology Department, Carnegie Mellon University , Pittsburgh, PA 15213, United States

Abstract

Abstract Motivation Analysis of time series transcriptomics data from clinical trials is challenging. Such studies usually profile very few time points from several individuals with varying response patterns and dynamics. Current methods for these datasets are mainly based on linear, global orderings using visit times which do not account for the varying response rates and subgroups within a patient cohort. Results We developed a new method that utilizes multi-commodity flow algorithms for trajectory inference in large scale clinical studies. Recovered trajectories satisfy individual-based timing restrictions while integrating data from multiple patients. Testing the method on multiple drug datasets demonstrated an improved performance compared to prior approaches suggested for this task, while identifying novel disease subtypes that correspond to heterogeneous patient response patterns. Availability and implementation The source code and instructions to download the data have been deposited on GitHub at https://github.com/euxhenh/Truffle.

Funder

National Science Foundation

National Institutes of Health

Publisher

Oxford University Press (OUP)

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